Yellow Fever Vaccination

Yellow fever is a mosquito borne haemorrhagic fever. It is one of the most lethal diseases, with a case fatality rate of 20-50%.¹

• The aetiological agent is a small single stranded RNA virus.
• Symptoms develop after 3-6 days incubation.
• One in seven people infected develop a rapidly progressing illness characterised by hepatitis, renal failure, haemorrhagic and cardiovascular shock. Once infected, there is no treatment for yellow fever.
• It occurs particularly in sub-Saharan Africa, but also in tropical South America.
• Outbreaks occur on a regular basis and between 2000-2004 16 countries reported an epidemic.
• The reported incidence has been estimated to be approximately 10-500 times smaller than the true incidence. This has been estimated to be around 200,000 cases per year.²
• The virus is transmitted between wild monkeys and mosquitoes and cannot be eradicated.
• Vaccination is the best method of preventing and controlling the disease.

• The 17D live attenuated vaccine was developed in 1936 and became widely available in 1951.
• Wherever high vaccination rates have been achieved the incidence of Yellow fever has declined.
• Expansion of travel to these areas has increased demand for the vaccine and every year there are shortages.

• It is administered as a single dose by deep subcutaneous route and provides immunity in 95-100% of travellers.⁴
• Immunity probably persists for life, but re-vaccination is advised after 10 years for those whose risk of contracting the disease persists.⁵
• The vaccine can only be given at specialist centres.
• Many countries require an International Certificate of Vaccination either for all travellers or for those from an endemic country. The certificate is valid from the tenth day after primary vaccination and lasts for 10 years.
• Live vaccines can be given at the same time as inactivated ones.
  Other live vaccines can be administered at the same time as yellow fever vaccine, but must be given at different sites and in different syringes.
  If they are not given on the same day, they should be separated by an interval of at least 3 weeks.
• It is good practice to obtain written or verbal consent, prior to vaccination.
• Patient details, together with date, time, batch number and site of vaccination should be recorded, and an immunisation certificate issued, which is signed by patient and stamped by issuing centre.

• Anaphylaxis or serious hypersensitivity reactions:
  • It should not be given to those who have had a confirmed anaphylactic reaction within 72 hours of a previous dose of the same vaccine.^6,7
  • Confirmed reaction to a constituent of the vaccine. A history of oral intolerance to eggs or chicken protein. These patients should have allergy testing with diluted vaccine, and have de-sensitisation procedure if necessary.
• Immunosuppression, whether congenital, idiopathic or as a result of treatment with systemic steroids (excluding standard dose of topical or inhaled steroids), radiotherapy or cytotoxic drugs. Solid organ transplant recipients should not receive live vaccine.⁸
• History of thymus dysfunction (including thymoma, thymectomy) - thymic disorders predispose to viscerotropic adverse events.
• Symptomatic HIV infection, or HIV positive with signs of impaired immunity.
• Current severe febrile illness.
• Breastfeeding - The WHO have recommended that the vaccine is used with caution in breast-feeding mothers. In the UK the labelling states this is a contra-indication.
• Other severe adverse reactions. This means an extensive area of redness and swelling affecting a large area of the arm or leg, accompanied by a fever of 39.5° or higher, within 48 hours of the injection.
• Age is a relative contraindication:
  • In patients aged 60 or older, the risk of viscerotropic adverse events is increased (see below) - carefully consider the benefits of vaccination in the context of the patient's risk for exposure to yellow fever virus based on the destination.
  • Age less than 6 months.⁷

The following DO NOT contraindicate vaccination:

• A personal or family history of asthma, allergy, hay fever or eczema
• Prematurity
• Stable neurological conditions e.g. cerebral palsy, Down's syndrome or epilepsy
• Contact with infectious disease
• Treatment with antibiotics or local corticosteroids
• A child who is being breast fed, or a mother who is pregnant
• Being underweight
• Taking replacement corticosteroids

• Acute illness - Postpone immunisation until recovered. Minor infections, without fever or systemic upset are not reasons to postpone.⁶
• Pregnancy - The WHO and the Advisory Committee on Immunisation Practice recommend that live vaccines should be used only when the benefits clearly outweigh the risks .There is a much lower sero-conversion rate.⁹ Vaccination whilst pregnant is NOT an indication for abortion.
• Immunosuppression - Live vaccines can be given. However, these individuals may not be able to mount a full immune response. They may also suffer severe adverse reactions (see below). People at risk include patients receiving chemotherapy or generalised radiotherapy; patients on systemic corticosteroids for one week (high dose) or long term low dose.

The most commonly reported symptoms include:

• Headache, fatigue and malaise. These are also commonly reported by placebo patients.¹⁰
• Injection site erythema
• Acute meningo-encephalitis. The disease is self-limiting, though long-term sequelae have been noted.¹¹
• Yellow fever vaccine associated neurotropic disease (YEL-AND) e.g. Guillain-Barre, Bell's palsy, optic neuritis.^12,13 This suggests the vaccine may elicit auto immune reactions - and is commoner in those over 60 years of age.
• Yellow fever vaccine associated viscerotropic disease (YEL-AVD) This rare reaction was first recognised in 1996. It is characterised by hepatitis and multi-organ failure, like wild yellow fever. It also has similarly high fatality rates. There have been 23 cases. There is a genetic basis to susceptibility for this. Also advanced old age and a history of thymic disease or related conditions e.g. myasthenia gravis have been implicated.^13,14

Whilst there is concern about the potential severity of these adverse events, it should be emphasised that Yellow fever vaccine is highly effective and that the benefits far outweigh the risks. However there have been calls for the development of a new inactivated (and so safer) vaccine.¹⁵